Development and validation of a selective, sensitive and stability indicating UPLC-MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance.

In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm×2.1mm, 1.7µm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp-I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis.

Reactive arthritis in tuberculosis: A case of Poncet's disease.

Reactive arthritis and erythema are uncommon presentations of tuberculosis (TB). Reactive arthritis in tuberculosis (TB) is known as Poncet's disease, a rare aseptic form of arthritis observed in patients with active TB. We report a case of Poncet's disease in a 20-year old man whose reactive arthritis overshadowed other clinical symptoms of TB resulting in delayed diagnosis and treatment. Although a conclusive diagnosis of Poncet's disease is not possible, reactive immunologic reactions such as reactive arthritis and erythema nodosum even without respiratory symptoms should raise suspicion on possible TB. Thus, taking a thorough medical history as well as performing relevant examinations and investigations for possible TB will help expedite the diagnostic process.

Reactive arthritis in tuberculosis: A case of Poncet’s disease

Reactive arthritis and erythema are uncommon presentations of tuberculosis (TB). Reactive arthritis in tuberculosis (TB) is known as Poncet’s disease, a rare aseptic form of arthritis observed in patients with active TB. We report a case of Poncet’s disease in a 20-year old man whose reactive arthritis overshadowed other clinical symptoms of TB resulting in delayed diagnosis and treatment. Although a conclusive diagnosis of Poncet’s disease is not possible, reactive immunologic reactions such as reactive arthritis and erythema nodosum even without respiratory symptoms should raise suspicion on possible TB. Thus, taking a thorough medical history as well as performing relevant examinations and investigations for possible TB will help expedite the diagnostic process.

Predictors of health related quality of life in older people with non-communicable diseases attending three primary care clinics in Malaysia.

OBJECTIVES: To determine the health related quality of life and its predictive factors among older people with non-communicable diseases attending primary care clinics. DESIGN: Cross-sectional study. SETTING: Three public primary care clinics in a district in Selangor, Malaysia. PARTICIPANTS: Registered patients aged 55 years and above. MEASUREMENTS: A face-to-face interview was conducted using a validated questionnaire of Medical Outcome Study 36-item short form health survey (SF-36). The outcome measure was the health related quality of life (HRQoL) and other factors measured were socio demography, physical activity, social support (Duke-UNC Functional Social Support Questionnaire), and presence of non-communicable diseases. RESULTS: A total of 347 participants had non-communicable diseases which included hypertension (41.8%), type 2 diabetes (33.7%), asthma (4.8%), hyperlipidaemia (1.7%), coronary heart disease (1.2%), and osteoarthritis (0.2%). Age ≥ 65 years old (OR =2.23; 95%CI=1.42, 3.50), single (OR=1.75; 95%CI=1.06,2.90), presence of co-morbid condition (OR=1.66; 95%CI=1.06, 2.61), and poorer social support (OR=2.11; 95%CI=1.27, 3.51; p=0.002) were significant predictors of poorer physical component of HRQoL . In predicting lower mental health component of HRQoL, the significant predictors were women (OR=2.28; 95%CI=1.44, 3.62), Indian ethnicity (OR=1.86; 95%CI=1.08, 3.21) and poorer social support (OR=2.71; 95%CI=1.63, 4.51). No interactions existed between these predictors. CONCLUSION: Older people with non-communicable diseases were susceptible to lower health related quality of life. Increasing age, single, presence of co-morbid conditions, and poorer social support were predictors of lower physical health component of HRQoL. While the older women, Indian ethnicity and poorer social support reported lower mental health component of HRQoL.

Ethnic differences in glycaemic control and complications: the adult diabetes control and management (ADCM), Malaysia.

INTRODUCTION: Ethnicity is an important factor in diabetes care. The understanding of its effect in this country may help to improve diabetes care, glycaemic control and diabetic complication rates. This study was to determine the diabetes control profile in relation to complication rates between the three main ethnics group in Malaysia. METHODS: This nested cross-sectional study was part of the Audit of Diabetes Control and Management (ADCM), an ongoing cohort patient registry focused on diabetes control and management in the primary care setting in Malaysia. This registry registers all diabetes patients aged 18 years old and above. Demographic data, diabetes duration, treatment modalities, as well as various risk factors and diabetes complications are reported. Data was handled by statisticians using STATA version 9. RESULTS: A total of 20330 patients from 54 health centers were registered at the time of this report. The majority were type 2 diabetics (99.1%) of whom 56.6% were female. The mean age was 57.9 years (SD 11.58). Malay accounted for 56.3%, Chinese 19.5% and Indian 22.5%. There were 30.3% who attained HbA1c < 7%. Among three main races more Chinese had HbA1c < 6.5% (Chi-square: X2 = 71.64, p < 0.001), but did not show less complications of nephropathy (Indian suffered significantly more nephropathy, Chi-square: X2 = 168.76, p < 0.001), ischaemic heart disease (Chi-square: X2 = 5.67, p = 0.532) and stroke (Chi-square: X2 =15.38, p = 0.078). CONCLUSION: This study has again emphasized the existence of ethnic differences in glycaemic control and complication profiles. The Chinese diabetics suffer as many diabetes-related complications despite better glycaemic control. Further studies will need to look into other socio-genetic factors in order to provide a more personalized effective diabetes care.

Cross-sectional study of older adults with type 2 diabetes mellitus in two rural public primary healthcare facilities in Malaysia.

Knowledge of the characteristics of older adults with type 2 diabetes mellitus (T2DM) is indispensible for improvement of their care. A cross-sectional study in two rural public primary healthcare centres in Malaysia identified 170 actively engaged older patients with T2DM, with suboptimal glycaemic control and frequent hypoglycaemia. The prevalence of multiple co-morbidities, complications of T2DM, high cardiovascular risk, neurological, musculoskeletal and visual deficits suggested high risk of disabilities and dependency but not yet disabled. This short window for interventions presents as an opportunity for development of a more comprehensive approach extending beyond glycaemia control to risk management, preventing functional loss and continuity of social participation.

Cushing's Syndrome Secondary to Adulterated Complementary and Alternative Medicine.

This is a case of a 65 year old lady who presented with Cushing's syndrome secondary to ingestion of a complementary and alternative medicine that has been adulterated with exogenous glucocorticoids. In a clinical consultation, it is important to include assessment of complementary and alternative medicine use for a comprehensive care.

Cushing's Syndrome secondary to adulterated complementary and alternative medicine

This is a case of a 65 year old lady who presented with Cushing’s syndrome secondary to ingestion of a complementary and alternative medicine that has been adulterated with exogenous glucocorticoids. In a clinical consultation, it is important to include assessment of complementary and alternative medicine use for a comprehensive care.

Reversible cortical blindness following successful surgical repair of two stab wounds in the heart.

This report describes a case of cortical blindness that followed successful surgical repair of two stab wounds in the heart in a 29-year old Libyan man. The patient presented in a state of pre cardiac arrest (shock and low cardiac output status), following multiple chest stab wounds. Chest tube was immediately inserted. Surgery was urgently performed suturing the two wounds; in the root of the aorta and in the left ventricle, and haemostasis was secured. Cardiac arrest was successfully prevented. The patient recovered smoothly, but 24 hours later he declared total blindness. Ophtalmic and neurological examinations and investigations that included fundoscopy, Electroencephalograms (EEGs) and Computed Tomography Scans revealed no abnormalities, apart from absence of alpha waves in the EEGs. We diagnosed the case as cortical blindness and continued caring for the patient conservatively. Three days later, the patient regained his vision gradually and was discharged on the 7(th) postoperative day without any remarks.

Reversible Cortical Blindness Following Successful Surgical Repair of Two Wounds in the Heart

This report describes a case of cortical blindness that followed successful surgical repair of two stab wounds in the heart in a 29-year old Libyan man. The patient presented in a state of pre cardiac arrest (shock and low cardiac output status); following multiple chest stab wounds. Chest tube was immediately inserted. Surgery was urgently performed suturing the two wounds; in the root of the aorta and in the left ventricle; and haemostasis was secured. Cardiac arrest was successfully prevented. The patient recovered smoothly; but 24 hours later he declared total blindness. Ophtalmic and neurological examinations and investigations that included fundoscopy; Electroencephalograms (EEGs) and Computed Tomography Scans revealed no abnormalities; apart from absence of alpha waves in the EEGs. We diagnosed the case as cortical blindness and continued caring for the patient conservatively. Three days later; the patient regained his vision gradually and was discharged on the 7th postoperative day without any remarks

The nutritional status of 1081 elderly people residing in publicly funded shelter homes in Peninsular Malaysia.

OBJECTIVES: The aim of this study was to determine the: (1) prevalence of undernutrition as determined by the 'DETERMINE Your Nutritional Health Checklist' (NHC) and (2) factors independently associated with undernutrition among the older residents of these publicly funded shelter homes in Peninsular Malaysia. DESIGN: A total of 1081 elderly people (59%M) over the age of 60 y were surveyed using questionnaires determining baseline demographics, nutritional and cognitive status, physical function and psychological well-being. SETTING: Shelter homes, Peninsular Malaysia. RESULTS: In all, 41.4% (n = 447) were nourished (score <3), 32.1% (n = 347) at moderate risk (score between 3 and 5) and 26.6% (n = 287) were at high risk of undernutrition (score>5) according to the NHC. A large proportion of subjects were underweight with 14.3% of subjects recording a low body mass index (BMI) <18.5 kg/m2 and a further 18.2% recording a BMI between 18.5 and 20 kg/m2. The residential geriatric depression score (GDS-12R) (relative risk (RR) = 1.03 (95% confidence interval (CI) 1.01-1.05); P = 0.002) and the number of illnesses (RR = 1.14 (95% CI 1.07-1.21); P < 0.001) were found to be independently associated with nutritional risk (NHC score > or = 3). Using a BMI < 18.5 kg/m2 as an objective marker for nutritional risk, the NHC was shown to have a sensitivity of 66.4% (95% CI 58.0-74.2%), specificity of 42.7% (95% CI 39.3-46.1%), positive predictive value of 16.2% (95% CI 13.3-19.5%) and a negative predictive value of 88.4% (95% CI 84.9-91.4%). CONCLUSIONS: Many elderly people residing in publicly funded shelter homes in Malaysia may be at-risk of undernutrition, and were underweight. The NHC is better used as an awareness tool rather than as a screening tool.